Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

Abstract

To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.